Method of Making Drug-Elution Control Sleeve For Drug-Eluting Balloon

ABSTRACT

An apparatus, assembly and method for controlling release of a drug from a drug-eluting balloon during delivery of a drug-eluting balloon to a situs within a body. More particularly, the present invention relates to a diametrically expandable sleeve having a first non-diametrically unexpanded state in which drug retained on or in a drug-eluting balloon is protected from release by a sleeve and a second diametrically expanded state in which drug retained on or in the drug-eluting balloon is exposed for focal release in the body by diametric expansion of the sleeve, exposing openings in the sleeve during diametric expansion and closing the openings in the sleeve when the sleeve is in its diametrically unexpanded state.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application is a divisional of co-pending U.S. patentapplication Ser. No. 16/796,901 filed Feb. 20, 2020, now U.S. Pat. No.11,559,668 issued on Jan. 24, 2023, which claims priority to U.S.Provisional Patent Application Ser. No. 62/808,662 filed Feb. 21, 2019,both of which are incorporated by reference in its entirety.

BACKGROUND OF THE INVENTION

The present inventions relates generally to a device for controllingrelease of a drug from a drug-eluting balloon during delivery of thedrug-eluting balloon to a situs within a body. More particularly, thepresent invention relates to a diametrically expandable sleeve having afirst non-diametrically unexpanded state in which drug retained on or ina drug-eluting balloon is protected from release and a seconddiametrically expanded state in which drug retained on or in thedrug-eluting balloon is exposed for focused localized release in thebody.

Drug-eluting balloon catheters are frequently used in treating diseasedvasculature, particularly the coronary and peripheral vasculature.Drug-eluting balloon catheters also have potential application in otheranatomic passageways, including, without limitation, coronary valves,atrial or ventricular chambers of the heart, with neuro-interventionalpathologies, within the perivascular spaces in the brain, in thesubarachnoid or subdural spaces or within the spinal canal.

Localized pathologies, such as vascular disease, often respond morefavorably to focal treatment at the localized site of the pathologyrather than systemic treatment. Thus, it is desirable to provide adrug-eluting balloon device that safeguards against premature release ofdrug during delivery or deployment of the drug-eluting balloon device.

A primary difficulty with current drug-eluting balloons is that the drugis subjected to washout by the blood flow either during navigating thetortuous passageways to a delivery site or at a delivery site. Drugwashout reduces the amount of drug present for therapeutic delivery atthe desired situs within the body as a result of loss of drug in theblood flow. Washout also creates the risk of broader systemic drugeffects. Thus, it is highly desirable to provide an improved drugeluting balloon delivery system and method that safeguards against drugwashout and permits focused localized delivery to the desired situswithin the body.

Current drug-eluting balloons typically fall in two general classes.First are porous balloons that delivery a drug infused through acatheter into a space within the balloon and through the porous wall ofthe balloon. Second are balloons having a smooth outer surface with acoating layer, such as a hydrogel or other polymer, capable of retainingthe drug and allowing the drug to elute from the coating layer.

Several attempts have been made to protect the outer surface of adrug-eluting balloon during delivery and deployment with retractablesheaths or cages configured to act as a spacer between the balloonsurface and the vascular tissue. These devices, however, do not appearto solve the technical problems of increased device profile,longitudinal flexibility for trackability while navigating tortuousvascular passageways, and restricting the premature release of drug fromthe balloon. Moreover, none of the current devices employ an elutionsleeve which is configured to have a first substantially two-dimensionalsmooth delivery surface profile in which openings in the elution sleevehave dimensions configured to prevent drug from eluting through theopenings when the balloon and sleeve are in a first diametricallyunexpanded state during delivery of the balloon to a situs within thebody and a second substantially three-dimensional surface profile whenthe balloon and sleeve are in a second diametrically expanded state atthe situs within the body. The substantially two-dimensional surfaceprofile is characterized by substantially all of the elongate membershaving outer surfaces laying substantially co-planar with each otherwhen the sleeve is in an unexpanded diametric state. When the sleeve isin a diametrically expanded state, the substantially three-dimensionalsurface profile is characterized by having at least some of the elongatemembers having at least a portion of their outer surfaces projecting outof plane relative to other portions of the elongate members. The out ofplane position of the elongate members may assume a wide number ofgeometries that impart a surface texture to the sleeve. Such surfacetextures may include the elongate members assuming a sinusoidal,undulating or saw-tooth shape in the Z-axis of the sleeve projectingradially outward from the central longitudinal axis of the catheter.

In the three-dimensional surface profile, the elongate members of thesleeve will have deformed and at least a portion of the elongate memberswill have angularly rotated about their axes such that a lateral surfaceof an elongate member will be positioned to project outward from thesleeve. In this outwardly projecting position, the Z-axis thickness ofan elongate member is outwardly exposed and, when the sleeve is expandedagainst a diseased surface in the body, such as vascular plaque, theelongate member acts as a cutting surface to penetrate into the diseasedtissue. This penetration of the elongate member into the diseased tissueis quite small, typically less than the width of an elongate member, yetthe penetration provides a focused pathway into the diseased tissue forpenetration of a drug released from an underlying drug-eluting balloon.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a diametricallyexpandable sleeve for covering a drug-eluting balloon during handling,delivery and deployment that substantially encloses the drug-elutingballoon and prevent drug on or in the balloon from releasing from theballoon when the balloon is in its diametrically unexpanded state andwhich opens upon diametric expansion of the sleeve to allow focused drugrelease through the sleeve from the balloon.

It is a further object of the present invention to provide adrug-elution sleeve which is capable of pseudoelastic deformation underthe influence of balloon inflation pressures.

It is another objective of the present invention to provide adrug-elution sleeve made of a shape memory or superelastic metal,pseudometal or polymer having a thickness between greater than or equalto 0.1 μm and less than or equal to 75 μm.

It is yet another objective of the present invention to provide adrug-elution sleeve in which a pattern of slits that define elongatestrut members of the drug-elution sleeve, with the pattern of slitsimparting both longitudinal and circumferential compliance to thedrug-elution sleeve as well as allow for geometric deformation of theslits during diametric expansion of the drug-elution sleeve.

It is still another objective of the present invention to provide adrug-elution sleeve in which a plurality of slits pass through athickness of the sleeve and have a width less than or equal to 25 μmwhen the sleeve is in its diametrically unexpanded state.

It is yet still another objective of the present invention to provide adrug-elution sleeve in which a plurality of slits passing through thethickness of the sleeve each have a length greater than 1 mm.

It is another objective of the present invention to provide adrug-elution sleeve in which the plurality of slits passing through thethickness of the sleeve have an aspect ratio of length to width greaterthan or equal to 1:500.

It is still another objective of the present invention to provide adrug-elution sleeve in which the plurality of slits have an aspect ratioof less than or equal to 1:120.

It is still another objective of the present invention to provide adrug-elution sleeve having a proximal and/or distal attachment regionconfigured to attach the drug-elution sleeve to a catheter andsurrounding a drug-eluting balloon.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a side elevational view of a drug-elution sleeve mounted on aballoon catheter in an unexpanded diametric state in accordance with thepresent invention.

FIG. 1B is a side elevational view of the drug-elution sleeve mounted ona balloon catheter in an expanded diametric state in accordance with thepresent invention.

FIG. 2 is a plan view of a slit pattern for the drug-elution sleeve inaccordance with the present invention.

FIG. 3A is a side elevational view of a drug-elution sleeve in itsunexpanded diametric state in accordance with the present invention.

FIG. 3B is a side elevational view of drug-elution sleeve in an expandeddiametric state in accordance with the present invention.

FIG. 3C is an enlarged view of region 3C of FIG. 3B.

FIG. 4 is a plan view of an alternative slit pattern for thedrug-elution sleeve in accordance with the present invention.

FIG. 5 is an enlarged view of a drug-elution sleeve made in accordancewith the slit pattern of FIG. 4 .

FIG. 6 is a section of an alternative embodiment of the drug-elutionsleeve in its unexpanded diametric state in accordance with the presentinvention.

FIG. 7 is a section of the alternative embodiment of the drug elutionsleeve shown in FIG. 6 in an expanded diametric state in accordance withthe present invention.

FIG. 8 is a section of another alternative embodiment of thedrug-elution sleeve in its unexpanded diametric state in accordance withthe present invention.

FIG. 9A is a diagrammatic cross-sectional view of a drug-eluting ballooncatheter and the drug elution sleeve in diametrically unexpanded statein accordance with the present invention.

FIG. 9B is a diagrammatic cross-sectional view, taken along line 9B-9Bof FIG. 1 , of a drug-eluting balloon catheter and drug elution sleevein a diametrically expanded state.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention will be described with reference to theaccompanying Figures, in which like elements are identified by likereference numerals. While the present invention will be described withreference to certain preferred embodiments, those of ordinary skill inthe art will understand and appreciate that variations in materials,structure, material properties, and tolerances may be made withoutdeparting from the scope of the invention, which is limited only by theclaims appended hereto and their range of equivalents.

For purposes of clarity, the following terms used in this patentapplication will have the following meanings:

“Substantially” is intended to mean a quantity, property, or value thatis present to a great or significant extent and less than and includingtotally.

“About” is intended to mean a quantity, property, or value that ispresent at ±10%.

“Pseudometallic” or “Pseudometal” is intended to mean a biocompatiblematerial which exhibits biological response and material characteristicssubstantially the same as biocompatible metals. Examples ofpseudometallic materials may include composite materials, ceramics,quartz, and borosilicate. Composite materials are composed of a matrixmaterial reinforced with any of a variety of fibers made from ceramics,metals, or polymers. The reinforcing fibers are the primary loadcarriers of the material, with the matrix component transferring theload from fiber to fiber. Reinforcement of the matrix material may beachieved in a variety of ways. Fibers may be either continuous ordiscontinuous. Reinforcement may also be in the form of particles.Examples of composite materials include those made of carbon fibers,boron fibers, boron carbide fibers, carbon and graphite fibers, siliconcarbide fibers, steel fibers, tungsten fibers, graphite/copper fibers,titanium and silicon carbide/titanium fibers.

“Pseudoelastic deformation” is intended to mean a deformation caused byan applied load that is completely recoverable upon removal of the loadand the limit of which is characterized by being significantly largerthan the elastic limit of a traditional metal (e.g., 8% strain in thecase of nitinol). This phenomenon is caused by a load or stress inducedsolid-state phase change that is reversible upon removal of the load.

“Shape memory alloy” is intended to mean a binary, ternary, quaternarymetal alloy that recover apparent permanent strains when raised above anAustenitic transformation temperature (A_(s)). Shape memory alloys havetwo stable phases, i.e., a high-temperature or austenite phase and alow-temperature or martensite phase.

“Superelastic” is intended to mean a property of a materialcharacterized by having a reversible elastic response in response to anapplied stress. Superelastic materials exhibit a phase transformationbetween the austenitic and martensitic phases as the applied stress isloaded or unloaded.

“Radiopaque” is intended to mean any material that obstructs passage ofradiation and increases background contrast in X-rays or similarradiation images.

A stress-strain curve for a shape memory or superelastic material, suchas austenitic nitinol, in which a sample is taken all the way to failureat a temperature above A_(f) (finish of Austenitic transformation) canbe separated into the following regions of the stress-strain curve:elastic deformation of austenite, pseudoelastic deformation of austeniteto stress induced martensite, elastic deformation of the stress inducedmartensite, plastic deformation of the stress induced martensite andfracture. Removal of the load at any point before the onset of plasticdeformation of the stress induced martensite will result in completerecovery of the deformation.

The sleeve of the present invention is preferably made of a shape memoryor superelastic material, including metals, pseudometals and polymers.Particularly preferred materials are binary, ternary or quaternarynickel-titanium based metal alloys, such as nitinol. Shape memory and/orsuperelastic metal alloys may be binary, ternary, quaternary, quinary orn-ary, where n-is an integer of the base value metal alloys. Whilebinary nickel-titanium alloys are well known in the art, other alloyadditions of iron, copper, chromium, vanadium, niobium, bismuth, cobalt,tungsten, platinum, palladium, tantalum, zirconium, hafnium and/or goldmay also be used. Certain radiopaque elements may, such as tungsten,bismuth, cobalt, or tantalum, may be employed, either as an alloyingelement or as a discrete layer in the sleeve, to increase the sleeve'sradiopacity.

When a nitinol alloy is employed, it is typically in a thermally-inducedmartensitic state where the material is brought to a temperature belowMf (finish of martensitic transformation) and subsequently kept belowA_(s) (onset of austenitic transformation). If the material issufficient deformed (greater than 0.5% strain) while in itsthermally-induced martensitic state and subsequently constrained attemperatures above A_(s), it is still considered to be in itsthermally-induced martensite state and not in a stress-inducedmartensite state. A stress-strain curve for martensitic nitinol in whicha sample is taken all the way to failure at a temperature below A_(s)can be separated into the following regions: elastic deformation ofthermally induced martensite, pseudoplastic deformation of thermallyinduced martensite via detwinning, elastic deformation of the detwinnedthermally induced martensite, plastic deformation of the detwinnedthermally induced martensite and fracture. Removal of the load at anypoint before the onset of plastic deformation of the detwinned thermallyinduced martensite will result in complete recovery of the deformationwhen heated above A_(f).

In accordance with its most general aspect, the present inventionrelates to a diametrically expandable sleeve concentrically coupled toan outer surface of a drug-eluting balloon. The sleeve is substantiallytubular and has a plurality of slits passing through the sleeve wallsthat geometrically deform from a closed position when the drug-elutingballoon and sleeve are in an unexpanded diametric state to an openposition when the drug-eluting balloon and sleeve are in a diametricallyexpanded state. When the sleeve is in a diametrically unexpanded stateand the slits are in their closed position, the slits have an open areaconfigure to restrict drug in or on the drug-eluting balloon frompassing through the slits. When delivered to a situs within a body andplaced in a desired location, the sleeve will be in apposition tobiological tissue. As the balloon is inflated, such as by infusion of apressurized fluid into the balloon, the sleeve will diametrically expandand the plurality of slits geometrically deform to their open position,the open areas of the slits expose the drug-eluting balloon beneath thesleeve. Once the exposed to the adjacent biological tissue, the drugcarried on the drug-eluting balloon will elute through the open slits tothe adjacent biological tissue. Upon deflation of the balloon, thesleeve will diametrically collapse on the balloon, with the plurality ofslits closing and reassuming their substantially closed position on theballoon.

The sleeve also has land regions between the plurality of slits thatgeometrically deform as the sleeve and drug-eluting balloon are expandedfrom the diametrically unexpanded state to the diametrically expandedstate. These land regions are typically elongate strut members havinghinge regions at opposing ends of the elongate strut members. Forpurposes of this application, the land regions will also be referred tosynonymously as elongate strut members. The hinge regions act as pivotpoints to distribute the strain associated with deformation of the landregions during diametric expansion and contraction of the sleeve. Eachof the land regions has a width, length and thickness. As the landregions are defined between adjacent slits, the width of a land regionis determined by the spacing of the slits. Land region widths may bebetween about 5 μm and about 50 μm, while lengths may be between 25 μmand 500 μm. Land region thickness will be equivalent to the thickness ofthe sleeve. The land regions will typically have generally quadrilateraltransverse cross sections with a luminal surface that faces the lumen ofthe sleeve, and abluminal surface that faces away from the lumen of thesleeve and lateral surfaces that face each of the slits adjacent to andbounding the land region, all when the sleeve is in its unexpandeddiameter. The plurality of land regions may each move in the X-Y planeof the sleeve and may also each move in the Z-axis of the sleeve byrotating about their individual axes. When each of the plurality of landregions rotate about their own axis, each land region assumes an twistedand arcuate configuration in which a lateral surface of each rotatedland region projects outwardly above the X-Y plane of the sleeve. Inthis manner the twisted and arcuate portion that projects radiallyoutwardly exposes a portion of the lateral surface of the land region,as opposed to the luminal or abluminal surface, to the biological tissueagainst which the sleeve and balloon are in apposition. The twisted andarcuate lateral surfaces of the land regions that project outwardly fromthe plane of the sleeve assist in penetrating or pressing into adjacentbiological tissue, such as vascular tissue, which, in turn, aids in drugabsorption into the biological tissue as it elutes from the drug-elutingballoon.

Turning now to the accompanying Figures, FIGS. 1A and 1B depict thedrug-eluting balloon assembly 10 of the present invention includes asleeve 12 mounted on an underlying drug-eluting balloon catheter 16. Thesleeve 12 has a proximal end 11 and a distal end 13 that are joined tothe drug-eluting balloon catheter 16 to couple the sleeve 12 to thedrug-eluting balloon catheter 16. FIG. 1A depicts the drug-elutingballoon assembly 10 in its unexpanded diametric state, whereas FIG. 1Bdepicts the drug-eluting balloon assembly 10 in its expanded diametricstate. A plurality of slits 14 are formed in the sleeve 12 and passthrough wall surfaces thereof. Each of the plurality of slits 14 areelongate along a longitudinal axis of the sleeve 12 and communicatebetween a luminal surface of the sleeve 12 and an abluminal surface ofthe sleeve 12. The plurality of slits 14 are arrayed in a pattern alongan intermediate section 17 of the sleeve 12. The intermediate section 17extends about the circumference of the sleeve 12 and about a substantialextent of the longitudinal axis of the sleeve 12. Proximal end 11 anddistal end 13 may be used to couple the sleeve 12 to the drug-elutingballoon catheter 16. The pattern of the plurality of slits 14 isconfigured to allow for geometric deformation of the plurality of slits14 as the sleeve 12 is diametrically expanded as the underlying balloon18 is inflated. During geometric deformation of the sleeve 12, the slits14 enlarge and open and the land regions 15 deform to expose thedrug-eluting balloon 18 beneath the sleeve 12.

The generally concentric positional relationship between the sleeve 12,the drug-eluting balloon 18, and the catheter 16 is shown in FIGS. 9Aand 9B. FIG. 9A illustrates the assembly in the substantiallydiametrically unexpanded state, whereas FIG. 9B illustrates the assemblyin the substantially diametrically expanded state. In FIGS. 9A and 9B,catheter 76 has a central lumen 74 and carries an inflatable balloon 78having a drug-eluting or drug coating 79 on an outer surface of theinflatable balloon 78. In its inflated state a fluid filled space 77 iscreated by introduction of an inflation fluid, not shown, through thelumen 74 of catheter 76. Sleeve 72 is disposed on an outer diametricsurface of the drug-eluting or drug coating 79. As previously described,sleeve 72 has a plurality of slits 74 and a plurality of land regions75. Upon diametric expansion of the balloon, as described above, theslits open under the influence of geometric deformation the sleeve 72,with the land regions assuming a rotated position about theirlongitudinal axes to project radially outward from the longitudinal axisof the sleeve 72, balloon 78 and catheter 76 to expose the drug-elutingor drug coating 79 to adjacent tissue. Upon release of the expansiveforce, e.g., due to expansion of balloon 78, the sleeve 72 returns toits unexpanded state with the plurality of land regions 75 returning toa non-rotated state lying substantially normal to the plane of the outersurface of the sleeve 72 as depicted in FIG. 9A.

Both the geometry and arrangement of the plurality of slits 14 may havemany different configurations. The plurality of slits will typically beelongate slits. Each of the plurality of slits 14 will have a depth thatpasses entirely through the wall thickness of the sleeve 12, a length,and a width sufficient to allow the slits to be substantially closed toprotect the balloon 18 and drug on the balloon 18 during delivery andopen during radial expansion of the sleeve 12 to expose the balloon 18and the drug coating on the balloon to allow the drug to elute throughthe open slits 14. Exemplary, non-limiting widths of each of theplurality of slits is between about 0.5 μm and about 10 μm. The width ofthe plurality of slits 14 may be uniform or variable along the lengthand circumference of the sleeve 12. The length of each of the pluralityof slits 14 may be highly variable and be between about 25 μm to overabout 500 μm. Moreover, the length of each of the plurality of slits 14may be or may not be uniform along the longitudinal and circumferentialaxes of sleeve 12. For example, a first circumferential row of slits 14may have a first length, whereas a second circumferential row of slits14 may have a second length, with the second length is either greaterthan or less than the first length. The lengths of the slits 14 may bethe same or vary along the longitudinal axis of the sleeve 12. Each slit14 in a given circumferential row of slits 14, however, should have thesame length to assure substantially uniform radial expansion of thatgiven circumferential row of slits 14 and the entire sleeve 12. Thesleeve 12 of FIGS. 1A and 1B is shown in a flattened plan view in FIG. 2.

Further, the plurality of slits 14 may be substantially linear, may havea substantially linear section with an offset section that is orientedhelically relative to the circumferential and longitudinal axes of thesleeve 12 or may have a substantially linear section, an intermediatehelically oriented offset section and a second substantially linearsection as shown in FIG. 6 . Optionally, as shown in FIGS. 6-8 , atleast some and/or all of the plurality of slits may have terminal strainrelief sections on either end of the slit 14 or on both ends of eachslit 14. The terminal strain relief sections may be configured as arounded terminal end having substantially the same or greater diameterthan the width of the slit 14.

With reference to FIG. 2 , a plurality of elongate slits 24 are formedin the sleeve 20 and pass through an entire wall thickness of sleeve 20.The plurality of elongate slits 24 are patterned in sleeve 20 impartboth longitudinal and circumferential compliance to sleeve 20 as well asallow for geometric deformation of the slits during diametric expansionof the sleeve 20 under the influence of balloon expansion. In accordancewith one aspect of the invention, the sleeve 20 has a substantiallyuniform wall thickness between greater than or equal to 0.1μ and lessthan or equal to 75μ. In this manner, the depth of each of the pluralityof elongate slits 24 is also between greater than or equal to 0.1μ andless than or equal to 75 such that each of the plurality of elongateslits 24 is open to a luminal or inner surface of sleeve 20 and anabluminal or outer surface of sleeve 20 along substantially the entirelength of each of the plurality of elongate slits 24. When sleeve 20 isin its diametrically unexpanded state, each of the elongate slits 24have a width less than about 25 μm, preferably less than 15 μm, morepreferably less than 10 μm, and most preferably between about 1 μm and 5μm. Similarly, when sleeve 20 is in its diametrically unexpanded state,each of the plurality of elongate slits 24 preferably have a lengthgreater than about 1 mm. In accordance with an embodiment of theinvention, each of the plurality of elongate slits 24 have a width tolength aspect ratio greater than or equal to about 1:500 to about 1:120.

Between circumferentially adjacent elongate slits 24 are land areas,synonymously referred to as elongate strut members, 15. Land areas 15act as the structural scaffold for sleeve 20, forming elongate strutmembers, and deform in the X-Y plane of the sleeve 20 during radialexpansion of the sleeve 20 under the influence of balloon inflation.Additionally, depending upon the configuration of the plurality of slits24, the land areas 15 may also deform in the Z axis of sleeve 20, suchas by at least partially rotating about their individual axes. Hingeregions 27 are present between longitudinally adjacent pairs of theplurality of elongate slits 24 and are positioned at opposing terminalends of each of the plurality of slits 24. Hinge regions 27 act as hingepoints for each of the land areas 15 during radial expansion of thesleeve 20.

Circumferential rows 24 a, 24 b of slits 24 are arrayed along thelongitudinal axis of the sleeve 20. The circumferential rows 24 a, 24 bmay be staggered such that a first set of circumferential rows 24 a ofslits 24 are longitudinally offset from a second row of circumferentialrows 24 b of slits 24 each other along the longitudinal axis of thesleeve 20, with a slit 24 of circumferential row 24 b being at leastpartially positioned between adjacent pairs of slits 24 ofcircumferential row 24 a. For example, where all of slits 24 have thesame length, a slit 24 in circumferential row 24 b may have an endthereof positioned at about one-half the length of the adjacent slits 24in circumferential row 24 a on either side of the slit 24 ofcircumferential row 24 a. In this example, the hinge regions 27 will bepositioned with a periodicity along the length of the sleeve 20 which isone-half the length of each slit 24. Thus, if all slits 24 are 100 μm inlength, a slit 24 in circumferential row 24 b will have opposing endspositioned about 50 μm from ends of adjacent slits 24 in circumferentialrow 24 a. The hinge regions 27, in this case, will also be staggeredalong the longitudinal axis of the sleeve 20 with a periodicity of about50 μm or one-half the length of the slits 24.

Sleeve 20 further has a first end 21 and an opposing second end 23. Thefirst end 21 and the second end 23 from proximal and distal ends of thesleeve 20 and serve as attachment points to attach sleeve 20 to either aballoon or to catheter 16. Optionally, terminal rows of elongate slits24 at the first end 21 and the second end 23 extend to and open to eachrespective end 21, 23.

FIG. 3A depicts a side elevational view of an intermediate portion 17 ofsleeve 20 configured as a tubular sleeve 30 in its diametricallyunexpanded state and FIG. 3B depicts a side elevational view of an endportion of sleeve 20 configured as a tubular sleeve 30 in itsdiametrically expanded state. Like sleeve 20, tubular sleeve 30 has aplurality of elongate slits 34, a plurality of land regions 35 and aplurality of hinge regions 37. The plurality of hinge regions 37 arearranged in rows 34 a, 34 b extending about the circumference of thetubular sleeve 30 and adjacent rows 34 a, 34 b extending along thelongitudinal axis of tubular sleeve 30. The plurality of elongate slits34 are arranged a staggered configuration and arrayed in a first row 34a of elongate slits 34 and a second row 34 b of elongate slits, each ofthe first row 34 a and the second row 34 b are staggered relative toeach other such that individual elongate slits 34 are interlaced betweenthe adjacent first row 34 a and second row 34 b about the entirecircumferential axis of the tubular sleeve 30 and along the longitudinalaxis of the tubular sleeve 30. In this manner, an end of each slit infirst row 34 a is adjacent intermediate regions of two circumferentiallyadjacent slits in second row 34 b. This interlaced pattern is repeatedalong the entire intermediate region 38 of tubular sleeve 30.Intermediate region 38 is positioned between opposing ends (not shown)of the tubular sleeve 30.

FIG. 3B depicts an end section of tubular sleeve 30 of FIG. 3A in adiametrically expanded condition where the plurality of slits 34 haveopened and at least some of the land areas 35, or elongate strutmembers, at least partially rotate about their longitudinal axes andassume an undulating or sinusoidal shape projecting above the normalplane of the outer wall surface of the tubular sleeve 30. The endsection of tubular sleeve 30 may, optionally, have terminal projections37. Terminal projections 37 may simply be extensions of the land areas35, or elongate strut members, which do not have any of slits 34.Terminal projections 37 may serve as anchors to affix the tubular sleeve30 to the catheter 16 or to the balloon 18.

FIG. 3C is an enlarged view of a section of tubular sleeve 30 in adiametrically expanded condition. The plurality of slits 34 are openedand the land areas 35, or elongate strut members, are at least partiallyrotated about their longitudinal axes. Each of the plurality of slits 34terminate at a hinge region 37 and opposing ends of each of theplurality of slits 34. Each hinge region 37 functions to allow the landareas 35, or elongate strut members, deform in both the X, Y and Z-axisof the tubular sleeve 30 upon diametric expansion of the tubular sleeve30 under the influence of inflation of balloon 18.

FIGS. 4 and 5 depict a high density tubular sleeve 40 embodiment inwhich the plurality of slits 44 have a higher pattern density relativeto that in tubular sleeve 30, with a corresponding higher patterndensity of the land areas 45, or elongate strut members, and the hingeregions 47. The pattern configuration of the plurality of slits 44 inhigh density tubular sleeve 40 are generally similar to theconfiguration of the plurality of slits 34, but have a lower width tolength aspect ratio than in tubular sleeve 30. Like tubular sleeves 20,30, high density tubular sleeve 40 geometrically deforms with theplurality of slits 44 enlarging and opening and land regions 45geometrically deforming along their length at hinge regions 47 toaccommodate opening of the plurality of slits 44. Similarly, theplurality of slits 44 and land regions 45 return to a substantiallyclosed position when an applied force is released, such as by deflationof balloon 18.

Turning to FIG. 6 , another alternative embodiment tubular sleeve 50 isdepicted. Like tubular sleeve 30 and high density tubular sleeve 40,tubular sleeve 50 has a plurality of elongate slits 54 and a pluralityof land areas 55, or elongate strut members, between adjacent pairs ofelongate slits 54. The plurality of elongate slits 54 are arrayed in aninterlaced pattern such that a first set of elongate slits 54 a iscircumferentially and longitudinally offset from a second set ofelongate slits 54 b. At least some of the plurality of elongate slits 54have an intermediate curved section 53 positioned intermediate betweenopposing ends of the elongate slits 54. The intermediate curved section53 extends generally helically relative to the longitudinal andcircumferential axes of the tubular sleeve 50. Hinge regions 57 areformed by land areas 55 between longitudinally adjacent pairs of theelongate slits 54. Optionally, strain relief sections 59 may be providedat opposing ends of at least some of the plurality of elongate slits 54.When provided, strain relief sections 59 may be enlarged rounded ends atopposing ends of the elongate slits 54 and act to disburse strain fromthe land regions 55, or elongate strut members, to the hinge regions 57during diametric expansion of the tubular sleeve 50. Such enlargedrounded ends of the elongate slits 54 are commonly known as fillets,chamfers or key holes.

FIG. 7 depicts tubular sleeve 50 in a diametrically expanded state inwhich the plurality of slits 54 are enlarged and open to expose theunderlying balloon 18 (not shown). At least some of the plurality ofland regions 55 rotate about their longitudinal axes and raise above thenormal plane of tubular sleeve 50 to project in a generally sinusoidal,undulating or saw-tooth shape in the Z-axis of the sleeve 50 projectingradially outward from the central longitudinal axis of the catheter 16(not shown) and the tubular sleeve 50. The intermediate curved section53 of the plurality of slits 54 helps to facilitate the axial rotationof the land regions 55 about their longitudinal axis and projectingradially outward from the central longitudinal axis of the tubularsleeve 50. Upon removal of a diametrically expansive force, such asdeflation of the balloon 18 (not shown) the land regions 55 andplurality of slits 54 return to a substantially closed position and theland regions 55 return to their substantially normal non-projectingstate when the tubular sleeve 50 is in its at least substantiallynon-diametrically expanded state.

Finally, turning to FIG. 8 , another alternative embodiment of tubularsleeve 50 is depicted as tubular sleeve 60. Like tubular sleeve 50,tubular sleeve 60 is a substantially tubular member having a pluralityof slits 64, defining a plurality of land regions 65 between adjacentslits. At least some of the plurality of slits 64 have terminal strainrelief sections 69 at opposing ends of the slits 64. In tubular sleeve60, however, the plurality of slits 64 are arrayed in circumferentialrows that are not circumferentially interlaced. Rather, each of thecircumferential rows of the plurality of slits 64 are longitudinallyoffset from each other along the longitudinal axis of the tubular sleeve60. At opposing terminal ends of the tubular sleeve 60 are terminalextension members 61 that project proximally and distally from thetubular sleeve 60. For ease of illustration, only one set of terminalextension members 61 are shown in FIG. 8 . Terminal slits have a firstportion 63 a defined between terminal circumferential rows of the landregions 65 and a second portion 63 b defined between the terminalextension members 61 projecting from the opposing ends of tubular sleeve60. While first portion 63 a is depicted as narrower in width thansecond portion 64 b, the widths of 63 a and 64 b may be substantiallythe same or may be different depending upon device design considerationswhich are within the skill of one in the art. The terminal extensionmembers 61, like terminal projections 37 in FIG. 3B, may serve asanchors to affix the tubular sleeve 60 to the catheter 16 (not shown) orto the balloon 18 (not shown).

Terminal extension members 61 or terminal projections 37 may beaccomplished by any of a wide variety of bonding methods known in theart, including, without limitation, adhesive bonding, thermal bonding,reflowing a compatible material, or the like to join the terminalextension members 61 or the terminal projections 37 to the balloon 18(not shown) or the catheter 16 (not shown).

In all embodiments of the invention, the sleeve is made a shape memoryor superelastic metal, pseudometal or polymer. The sleeve may befabricated from a planar material rolled into a tubular configuration,which may be coiled or butt-joined, or fabricated from a tubularmaterial, in which case the tubular material is coherent and seamless.Preferably, the sleeve is fabricated from a precursor hypotube which maybe made by wrought fabrication techniques or physical vapor depositionfabrication techniques, both of which are known in the art. Physicalvapor deposition of shape memory alloys and/or superelastic alloys ontocylindrical mandrels to form coherent, seamless tubes is known in theart. Such processes are exemplified by U.S. Pat. Nos. 6,379,83,7,335,426, 9,640,359, each of which are hereby incorporated byreference. The plurality of slits in each of the embodiments may be madeby various techniques, including, without limitation, machining, such asby laser cutting or electrical discharge machining, lithography,chemical etching, or the like. Where the sleeve is deposited onto acylindrical mandrel, it is preferable that the plurality of slits beformed in the sleeve while the sleeve is on the cylindrical mandrel,then the mandrel released from the sleeve after forming the slits.

Those skilled in the art will understand and appreciate that theapparatus, system and method of the present invention have beendescribed with reference to exemplary embodiments thereof. Further,while the invention has been described with reference to such exemplaryembodiments, variations in dimensions or configuration of the sleeve,slits, land regions, terminal extension members, terminal projections,materials, material properties, or the like are expressly intended andcontemplated. The scope of the present invention is intended to belimited only by the claims appended hereto.

1. A method of making a balloon catheter comprising the steps ofproviding a balloon catheter having a central axis and an inflatableballoon; concentrically coupling a sleeve to the inflatable balloon,wherein the sleeve comprises a shape memory or superelastic materialhaving a plurality of elongate slits passing through the sleeve definingelongate strut members between adjacent pairs of the plurality ofelongate slits, the plurality of elongate slits assuming a substantiallyclosed position when the inflatable balloon is in an uninflated stateand assuming a substantially open position when the inflatable balloonis in an inflated state; wherein at least some of the elongate strutmembers are configured to at least partially rotate about theirrespective longitudinal axes and project radially outward relative tothe central axis of the catheter thereby forming an arcuate projectionfrom a normal plane of the sleeve and then return to a substantiallyco-planar position in the normal plane of the sleeve when the inflatableballoon is in the uninflated state.
 2. The method of claim 1, furthercomprising the steps of making the sleeve by physical vapor depositionof a shape memory metal onto a cylindrical substrate, forming a sleevehypotube, and forming the plurality of elongate slits passing throughthe sleeve.
 3. The method of claim 2, wherein the step of physical vapordeposition of a shape memory metal onto a cylindrical substrate furthercomprises sputtering the shape memory metal onto a cylindricalsubstrate.
 4. The method of claim 1, wherein the sleeve is coupled tothe catheter at proximal and distal ends of the sleeve.
 5. The method ofclaim 1, wherein the plurality of elongate slits further comprises afirst set of elongate slits and a second set of elongate slits, thefirst set of elongate slits and the second set of elongate slits beingcircumferentially off-set from each other about circumferential andlongitudinal axes of the sleeve.
 6. The method of claim 4, furthercomprising a drug coating on an outer surface of the inflatable balloonwhich resides beneath the sleeve when the inflatable balloon is in theuninflated state.
 7. The method of claim 1, wherein the sleeve has asubstantially uniform wall thickness between greater than or equal to0.1 μm and less than or equal to 75 μm.
 8. The method of claim 5,wherein each elongate slit of the plurality of elongate slits passthrough the wall thickness of the sleeve and have a width less than orequal to 25 μm when the sleeve is in an unexpanded state.
 9. The methodof claim 6, wherein each elongate slit of the plurality of elongateslits has a length greater than 1 mm.
 10. The method of claim 5, whereineach elongate slit of the plurality of elongate slits has a width tolength aspect ratio greater than or equal to 1:500.
 11. The method ofclaim 5, wherein each elongate slit of the plurality of elongate slitshas a width to length aspect ratio less than or equal to 1:120.
 12. Themethod of claim 7, wherein each elongate slit of the plurality ofelongate slits have terminal strain relief sections at opposing endsthereof.
 13. The method of claim 12, wherein each of the terminal strainrelief sections further comprises an enlarged rounded section having adiameter greater than a width of an elongate slit of the plurality ofelongate slits within which the terminal strain relief section isassociated.
 14. The method of claim 7, wherein each elongate slit of theplurality of elongate slits further comprises a circumferentially offsetsection intermediate opposing terminal ends of each elongate slit of theplurality of elongate slits.
 15. The method of claim 14, wherein atleast some of the elongate strut members project radially outward in anundulating manner from a central longitudinal axis of the catheter. 16.The method of claim 1, wherein the sleeve further comprises proximal anddistal couplings configured to couple the sleeve to the ballooncatheter.
 17. The method of claim 1, wherein the sleeve is radiopaque.18. A method of making a drug-eluting balloon catheter comprising thesteps of concentrically coupling a sleeve to at least one of a catheteror a drug-eluting balloon, the catheter or drug-eluting balloon having acentral axis and an inflatable balloon, wherein the sleeve comprises ashape memory or superelastic material having a plurality of elongateslits passing through the sleeve defining elongate land regions betweenadjacent pairs elongate slits of the plurality of elongate slits, theplurality of elongate slits having a first substantially closed positionand a second substantially open position when an expansive force isapplied to the plurality of elongated slits; and configuring at leastsome of the elongate land regions to at least partially rotate abouttheir respective longitudinal axes and project radially outward relativeto the central axis of the catheter or the central axis of thedrug-eluting balloon thereby forming a projection from a normal plane ofthe sleeve then return to a substantially co-planar position in thenormal plane of the sleeve when the inflatable balloon is in anuninflated state.
 19. The method of claim 18, further comprising thesteps of making the sleeve by physical vapor deposition of a shapememory or superelastic material onto a cylindrical substrate, forming asleeve hypotube, and forming the plurality of elongate slits passingthrough the sleeve hypotube.
 20. The method of claim 19, wherein thestep of physical vapor deposition of a shape memory metal onto acylindrical substrate further comprises sputtering the shape memorymetal onto a cylindrical substrate.
 21. The method of claim 18, furthercomprising the step of configuring the plurality of elongate slits as afirst set of elongate slits and a second set of elongate slits, thefirst set of elongate slits and the second set of elongate slits beingcircumferentially off-set from each other about circumferential andlongitudinal axes of the sleeve.
 22. The method of claim 20, furthercomprising the step of sputtering the shape memory metal to have asubstantially uniform wall thickness between greater than or equal to0.1 μm and less than or equal to 75 μm.
 23. The method of claim 21,further comprising the step of configuring each elongate slit of theplurality of elongate slits pass through a wall thickness of the sleeveto have a width less than or equal to 25 μm when the plurality ofelongate slits are in the first substantially closed position.
 24. Themethod of claim 18, further comprising the step of configuring eachelongate slit of the plurality of elongate slits to have a width tolength aspect ratio greater than or equal to 1:500.
 25. The method ofclaim 18, further comprising the step of providing terminal strainrelief sections at opposing ends of at least some of the plurality ofelongate slits.
 26. The method of claim 18, further comprising the stepof circumferentially offsetting a section of at least some of theplurality of elongate slits at opposing ends of each elongate slit ofthe plurality of elongate slits.
 27. The method of claim 18, furthercomprising the step of coupling the sleeve to the at least one of acatheter or a drug-eluting balloon at proximal and distal ends of thesleeve.
 28. The method of claim 18 wherein the sleeve is radiopaque.